The proposed research focuses on the possible relationships between reduced uteroplacental blood flow and toxemia of pregnancy. Since uteroplacental blood flow and systemic blood pressure during pregnancy may largely depend on the interactions between uteroplacental production of prostaglandin E and renin, the local and systemic effects of both hormones will be evaluated. Experiments in acute and chronic animal models will attempt to correlate changes in uteroplacental blood flow with the secretion rates of prostaglandin E and renin. Radiolabelled microspheres will be used to measure organ blood flow. Prostaglandin E and renin (as angiotensin I) concentrations will be measured with specific radioimmunoassays. Pharmacologic and surgical methods will be employed to devise an animal model of human pre-eclampsia. Circulating levels of prostaglandin E as well as renin will be measured in pregnant patients in an attempt to assess their role in blood pressure control during human pregnancy. Additional studies evaluating the role of local hormones in controlling the increased renal function associated with pregnancy are also in progress.